The laboratory is continuing efforts to find quantitative and/or qualitative protein variations in diseases affecting the central nervous system. As there are large variations in the concentration of proteins in body fluids and tissues we have concentrated our efforts on the development of methods for the detection of trace proteins. Through the use of high resolution two dimensional protein electrophoresis and our development of highly sensitive silver stains, capable of detecting 0.1 nanogram we have found significant quantitative plasma protein differences in schizophrenia, and Alzheimer's disease. One of the plasma proteins which is increased in the plasma of patients with these diseases has been identified as haptoglobin, an acute-phase protein. Variations in acute-phase proteins are often associated with inflammatory processes. To facilitate our analysis of protein alterations in disease states, the Laboratory has developed a relational database, in collaboration with the NCI, to provide a linkage between known disease-associated protein alterations and quantitative variations of plasma proteins separated by high-resolution electrophoresis. As high-resolution two dimensional protein electrophoresis allows the simultaneous evaluation of 1,500 to 3,000 proteins in complex solutions, such as the body fluids a relational database is essential for the analysis of qualitative and/or quantitative changes of these proteins in disease states. The laboratory has linked this database to other protein and genomic databases on the Internet.